Causal Association of Type 2 Diabetes Mellitus and Glycemic Traits With Cardiovascular Diseases and Lipid Traits: A Mendelian Randomization Study

Objective: We aimed to evaluate the causal effect of type 2 diabetes mellitus (T2DM) and glycemic traits on the risk of a wide range of cardiovascular diseases (CVDs) and lipid traits using Mendelian randomization (MR).

Methods: Genetic variants associated with T2DM, fasting glucose, fasting insulin, and hemoglobin A1c were selected as instrumental variables to perform both univariable and multivariable MR analyses.

Results: In univariable MR, genetically predicted T2DM was associated with higher odds of peripheral artery disease (pooled odds ratio (OR) =1.207, 95% CI: 1.162-1.254), myocardial infarction (OR =1.132, 95% CI: 1.104-1.160), ischemic heart disease (OR =1.129, 95% CI: 1.105-1.154), heart failure (OR =1.050, 95% CI: 1.029-1.072), stroke (OR =1.087, 95% CI: 1.068-1.107), ischemic stroke (OR =1.080, 95% CI: 1.059-1.102), essential hypertension (OR =1.013, 95% CI: 1.010-1.015), coronary atherosclerosis (OR =1.005, 95% CI: 1.004-1.007), and major coronary heart disease event (OR =1.003, 95% CI: 1.002-1.004). Additionally, T2DM was causally related to lower levels of high-density lipoprotein cholesterol (OR =0.965, 95% CI: 0.958-0.973) and apolipoprotein A (OR =0.982, 95% CI: 0.977-0.987) but a higher level of triglycerides (OR =1.060, 95% CI: 1.036-1.084). Moreover, causal effect of glycemic traits on CVDs and lipid traits were also observed. Finally, most results of univariable MR were supported by multivariable MR.

Conclusion: We provided evidence for the causal effects of T2DM and glycemic traits on the risk of CVDs and dyslipidemia. Further investigations to elucidate the underlying mechanisms are warranted.